Residues in the eighth transmembrane domain of the proton-coupled folate transporter (SLC46A1) play an important role in defining the aqueous translocation pathway and in folate substrate binding

Fourteen contiguous residues of the 8th transmembrane domain (pink) are accessible to MTSEA-biotin. Accessibility of six of these residues (Blue type:_AA_HLP_L) is blocked by folate substrate. A homology model in the inward- and outward- open conformations suggests that flexibility in the exofacial region during carrier cycling can account for the extended accessibility.75